To understand how information propagates in a vertebrate brain requires the ability to accurately control neural activity at the cellular scale in an intact brain. This proposal seeks to create a set of new light-driven technologies for studying the mechanisms involved in the propagation of coherent neural activity in the brain. Because coherent activity is a hallmark of epileptic seizures, this work has direct relevance to understanding epilepsy. Additionally, because substances of abuse modulate specific neural populations, our investigation of how modulating the excitability of particular neuronal populations may shed light on the mechanisms of action of abused substances and new methods of treatment. Specifically, we will synthesize small organic molecules that are capable of delivering neurotransmitters with pinpoint accuracy and timing to specific regions of the brain. These compounds will be used in zebrafish to control neural activity. We will also create modulators of gene expression that can be activated with light. One strategy will silence a gene of interest, whereas the other will be able to activate one. These light driven systems of gene expression will be used in zebrafish to study the development of the central nervous system. PUBLIC HEALTH RELEVANCE: The research in this proposal will provide a set of tools that will aid work to understand the mechanisms involved in the propagation of coherent neural activity in the brain and the modulation of particular neuronal populations. Coherent neural activity is a hallmark of epileptic seizures and substances of abuse modulate specific groups of neurons, so this work is relevant to understanding epilepsy and developing methods of treatment for drug abuse. It will also provide a set of tools to explore the role of certain genes in vertebrate development, which will impact work to understand diseases caused by developmental genetic defects.